This application is a K02 Independent Scientist Career Development Award submitted by R. Christopher Pierce, Ph.D. There are five major goals of the career development plan, which include: i) focusing more attention on Dr. Pierce's primary research program (funded by R01 DA15214, R.C. Pierce, PI), which is concentrated on delineating the neurochemical and biochemical changes in various limbic nuclei responsible for the reinstatement of cocaine-induced drug seeking; ii) increasing the scope of these studies to include imaging experiments in non-human primate subjects in order to evaluate changes in the CNS prior to, during and after periods of excessive cocaine intake; iii) learning the technical and methodological details associated with magnetic resonance imaging and magnetic resonance spectroscopy experiments, which will be required to complete the second goal. Goals ii and iii will be done in collaboration with Drs. James Rowlett and Itamar Ronen; iv) expanding Dr. Pierce's research program from a relatively single-minded focus on the behavioral pharmacology of cocaine to include issues related to the neurotoxicity produced by other drugs of abuse. Specifically, he will determine the functional consequences of MDMA-induced damage of central serotonin systems as well as potential toxic interactions between cocaine and MDMA; and v) learning new techniques from Dr. Bryan Yamamoto and Dr. Jean-Jacques Soghomonian related to measures of neurotoxicity (i.e. measures of free radical formation, lipid and protein oxidation, excitoxicity and terminal degradation) in the context of the MDMA-cocaine project. Dr. Pierce currently devotes 60% effort to research and 40% effort to teaching and administrative duties. If this application is funded, he will be released from 25% of his non-research duties such that 85% of his time will be devoted to research. This release time will allow Dr. Pierce to devote more attention to his existing research and also expand his research collaborations with Drs. Rowlett, Ronen, Yamamoto and Soghomonian, which will have a significant positive impact on his career development. [unreadable] [unreadable] [unreadable]